Forecasting individual progression trajectories in Huntington disease enables more powered clinical trials.

Variability in neurodegenerative disease progression poses great challenges for the evaluation of potential treatments. Identifying the persons who will experience significant progression in the short term is key for the implementation of trials with smaller sample sizes. We apply here disease course mapping to forecast biomarker progression for individual carriers of the pathological CAG repeat expansions responsible for Huntington disease. We used data from two longitudinal studies (TRACK-HD and TRACK-ON) to synchronize temporal progression of 15 clinical and imaging biomarkers from 290 participants with Huntington disease. We used then the resulting HD COURSE MAP to forecast clinical endpoints from the baseline data of 11,510 participants from ENROLL-HD, an external validation cohort. We used such forecasts to select participants at risk for progression and compute the power of trials for such an enriched population. HD COURSE MAP forecasts biomarkers 5 years after the baseline measures with a maximum mean absolute error of 10 points for the total motor score and 2.15 for the total functional capacity. This allowed reducing sample sizes in trial up to 50% including participants with a higher risk for progression ensuring a more homogeneous group of participants.

Weight gain and comorbidities associated with oral second-generation antipsychotics: analysis of real-world data for patients with schizophrenia or bipolar I disorder.

BACKGROUND: Many second-generation antipsychotics (SGAs) are associated with weight gain and cardiometabolic effects. Antipsychotic-associated weight gain is linked to treatment interruptions, potentially increasing risk of relapse and hospitalization. This retrospective study assessed clinically significant weight gain (CSWG), treatment interruptions, and development of cardiometabolic conditions in patients with schizophrenia (SZ) or bipolar I disorder (BD-I) following initiation of oral SGAs with moderate to high weight gain risk. METHODS: Patients with no prior use of moderate to high weight gain risk oral SGAs were identified from patient-level medical/pharmacy claims and electronic medical records (January 2013-February 2020; OM1 Real-World Data Cloud). Those with ≥ 1 weight measurement in both the 12 months preceding and 3 months after SGA initiation (index date) were analyzed for continuous changes in weight, CSWG (≥ 7% and ≥ 10% increases from baseline), treatment interruptions (switches/discontinuations), and development of cardiometabolic conditions. RESULTS: Median follow-up times in the SZ (n = 8174) and BD-I (n = 9142) cohorts were 153.4 and 159.4 weeks, respectively; 45.5% and 50.7% were obese at baseline. Mean (SD) percent weight increase during treatment was 3.3% (7.2) and 3.7% (7.0) for patients with SZ and BD-I, respectively, and was highest for underweight/normal weight patients (SZ: 4.8% [8.1]; BD-I: 5.5% [8.7]). More than 96% had treatment interruptions during follow-up, primarily discontinuations. CSWG and treatment interruptions occurred within a median of 13 and 14 weeks after treatment initiation, respectively. Of patients with CSWG and treatment interruptions, approximately 75% did not return to baseline weight during follow-up. Among those without baseline cardiometabolic conditions, 14.7% and 11.3% of patients with SZ or BD-I, respectively, developed ≥ 1 condition over 12 months post-index. Incidence was generally highest among those who were overweight/obese at baseline and those who experienced CSWG. CONCLUSIONS: In this analysis of real-world data, both weight gain and treatment interruptions occurred early in treatment for patients with SZ or BD-I. Treatment-associated weight gain persisted despite switching or discontinuing index treatment. Additionally, cardiometabolic morbidity increased within 12 months of treatment initiation. Patients with SZ or BD-I are at greater risk than the general population for cardiometabolic conditions; weight gain associated with SGAs may exacerbate these health risks.

Topical antioxidants protect the skin from chemical-induced irritation in the repetitive washing test: a placebo-controlled, double-blind study.

BACKGROUND: There is increasing evidence that reactive oxygen species play an important role in the development of both irritant and allergic contact dermatitis. OBJECTIVES: To assess the potential of topical antioxidants to prevent the development of experimentally induced irritant contact dermatitis. METHODS: We evaluated the effect of a cream containing a combination of antioxidants on sodium lauryl sulfate-induced irritant contact dermatitis in the repetitive washing test. As readout parameters for skin barrier function and cutaneous inflammation stratum corneum hydration, cutaneous blood flow and transepidermal water loss were assessed in 25 volunteers with bioengineering methods. RESULTS: In comparison with the cream base and a frequently used barrier cream, the antioxidant cream had high radical scavenging activity and effectively protected the skin from chemical-induced irritation. CONCLUSIONS: The superiority of the cream with antioxidants to the cream base suggests that reactive oxygen species, at least in part, play a role in the development of irritant contact dermatitis.